The present study was carried out to examine whether acute experimental myocardial infarction affects the sympathetic transmission to vessels and to the heart of pithed rats via a presynaptic mechanism and, if so, to check whether inhibitory presynaptic cannabinoid receptor(s) and endocannabinoids are involved in this response. In pithed and vagotomized rats, electrical stimulation (0.75 Hz, 1 ms, 50 V, 5 or 15 pulses for increases in heart rate or blood pressure, respectively) of the preganglionic sympathetic nerve fibers or intravenous injection of isoprenaline (0.1 nmol/kg) or noradrenaline (1 nmol/kg) increased heart rate and blood pressure by about 50 beats/min and 40 mmHg, respectively. Ligation of the left coronary artery reduced the electrically (as opposed to the chemically) induced tachycardic and pressor responses by about 30-40%. The inhibitory effect of myocardial infarction was prevented by the cannabinoid CB(1) receptor antagonist rimonabant but not by the CB(2) receptor antagonist SR 144528 and the vanilloid TRPV1 receptor antagonist capsazepine. The inhibitory effect of myocardial infarction was slightly enhanced by inhibitors of anandamide and 2-arachidonyl glycerol degradation, URB597 and JZL184, respectively. Rimonabant increased the myocardial infarction-induced mortality. Our results demonstrate that during the early phase of myocardial infarction the activation of presynaptic CB(1) receptors by endogenously formed cannabinoids contributes to the inhibition of the neurogenic tachycardic and vasopressor responses. Thus, the CB(1) receptor-mediated inhibition of the excessive noradrenaline release from the sympathetic nerve fibres innervating the heart and vessels might play a protective role in myocardial ischemia.